Creating New Possibilities for Patients to Live Their Lives
Transcript of Creating New Possibilities for Patients to Live Their Lives
Creating New Possibilities for Patients
to Live Their Lives
August 2020
© 2020 Concert Pharmaceuticals, Inc. All Rights Reserved.
Forward-Looking Statements
Any statements in this presentation about our future expectations, plans and prospects, including, among others,
statements about our expectations on the progress of clinical development of CTP-543 and CTP-692 and the
timing of availability of clinical trial data, and any other statements containing the words “anticipate,” “believe,”
“continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,”
“will,” “would” and similar expressions, constitute forward-looking statements within the meaning of The Private
Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-
looking statements as a result of various important factors, including: the uncertainties inherent in the initiation
and timing of future clinical trials, whether preliminary results from a clinical trial will be predictive of the final
results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials,
expectations for regulatory approvals, availability of funding sufficient for our foreseeable and unforeseeable
operating expenses and capital expenditure requirements, expectations with respect to the protection of our
intellectual property afforded by our patents and other factors discussed in the “Risk Factors” section of our most
recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission and in other filings that
we make with the Securities and Exchange Commission. In addition, any forward-looking statements included in
this presentation represent our views only as of the date of this presentation and should not be relied upon as
representing our views as of any subsequent date. We specifically disclaim any obligation to update any forward-
looking statements included in this presentation.
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Clinical Pipeline
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Product Candidate Lead Indications Phase 1 Phase 2 Phase 3 Market Worldwide Rights
CTP-543Deuterated ruxolitinib
CTP-692Deuterated D-serine
Alopecia Areata: Dose Ranging Completed
Phase 1 Crossover Completed
Additional CNS
Indications
Alopecia Areata: Dose Regimen Completed (8 BID vs 16 QD)
Phase 1 SAD/MAD Completed
Alopecia Areata: Dose Regimen Completed (12 BID vs 24 QD)
Alopecia Areata: Long Term Extension
Schizophrenia: Dose Ranging Ongoing
Alopecia Areata: Phase 3 Expected to Begin Q4 2020
CTP-543: Late Stage Asset for Alopecia Areata
• Initial target indication: moderate-to-severe alopecia areata
‒ Common autoimmune disorder causing partial or widespread loss of
hair on the scalp and/or body
‒ Opportunity to address important unmet medical need
• CTP-543 is a deuterated ruxolitinib analog, possessing a
differentiated, potentially superior PK profile
• FDA granted Breakthrough Therapy and Fast Track designations
for CTP-543
• IP estate provides protection into 2037
• Plan to initiate Phase 3 program in Q4 2020
‒ Phase 2 positive topline results reported: primary endpoint achieved
with 8 mg and 12 mg twice-daily doses CTP-543 Phase 2 Trial: Baseline vs. Week 24
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Alopecia Areata: A Devastating Autoimmune Disease
• Approximately 700,000 patients affected with alopecia areata in the U.S. at any given
time*
• Estimated 40+% of patients reported to have ≥ 50% loss of scalp hair*
• Chronic condition affecting women, men and children of all ages
• Disease profoundly impacts patients
‒ Associated with anxiety, depression and other autoimmune conditions
• No FDA-approved treatment options
• FDA PFDDI meeting held September 2017
‒ Strong patient advocacy
*Benigno M. Clinical, Cosmetic and Investigational Dermatology 2020Non-Trial Participants
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CTP-543: Phase 2 Dose Ranging Trial Complete
• Randomized 149 adult patients with moderate-to-
severe alopecia areata in a double-blind,
randomized, placebo-controlled trial
‒ At least 50% hair loss as measured by Severity of Alopecia
Tool (SALT)
‒ Primary Endpoint: 50% relative reduction in SALT at Week
24 from baseline
‒ Sequentially randomized to receive one of three doses of
CTP-543 (4, 8,12 mg BID) or placebo for 24 weeks
• Primary endpoint met with statistical significance for
8 mg and 12 mg doses at Week 24
‒ 12 mg responders average 86% SALT improvement
‒ 8 mg responders average 78% SALT improvement
• Patient Global Impression of Improvement scale
‒ 78% (12 mg BID) and 58% (8 mg BID) of patients rated
“much improved” or “very much improved” at Week 246
9 %
21%
47%
58%
0
10
20
30
40
50
60
4 mg BIDPlacebo 8 mg BID 12 mg BID
Patients with ≥ 50% Change in SALT Relative to Baseline
Responders at Week 24
*** P < 0.001 vs PBO
% P
atie
nts
per
Tre
atm
ent
Week 12 Week 24
Response Over Treatment Period: 8 mg BID
Baseline
Responders: ≥ 50% Change in SALT Relative to Baseline
7
0
10
20
30
40
50
60
Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
% P
atie
nts
pe
r T
rea
tme
nt
Placebo 4 mg BID 8 mg BID 12 mg BID
***
***
******
*** P < 0.001 vs PBO
* P < 0.05 vs PBO
21%
9 %
47%
58%
CTP-543 Phase 2: Patients Achieving SALT Score ≤ 20
• CTP-543 8 mg BID and
12 mg BID significantly
different from placebo on
percent of patients
achieving a SALT score
≤20 at 24 weeks
‒ SALT 20 indicates 80
percent or greater scalp hair
present
• SALT 20 is the primary
efficacy endpoint to be
utilized in Phase 3 studies
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CTP-543 Response Over Treatment Period: 12 mg BID
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Baseline Week 12 Week 24• 12 mg BID generally produced faster
onset and greater magnitude of
effect compared to 8 mg BID
• Eyebrow and eyelash involvement
not formally assessed
‒ Substantial regrowth observed
‒ Further assessments planned in
future trials
Baseline Week 24
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CTP-543 Phase 2 Dose Ranging TrialCommon (≥ 10%) Treatment Emergent Adverse Events (# Patients)
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Preferred Term PlaceboCTP-543
4 mg
CTP-543
8 mg
CTP-543
12 mg
Headache 4 (9.1%) 5 (17.2%) 10 (26.3%) 7 (19.4%)
Nasopharyngitis 1 (2.3%) 3 (10.3%) 3 (7.9%) 9 (25.0%)
URI 7 (15.9%) 2 (6.9%) 2 (5.3%) 7 (19.4%)
Acne 2 (4.5%) 4 (13.8%) 4 (10.5%) 6 (16.7%)
Nausea 4 (9.1%) 4 (13.8%) 4 (10.5%) 1 (2.8%)
Cough 0 4 (13.8%) 1 (2.6%) 2 (5.6%)
LDL increase 0 0 4 (10.5%) 0
Diarrhea 3 (6.8%) 3 (10.3%) 1 (2.6%) 0
Folliculitis 0 3 (10.3%) 2 (5.3%) 1 (2.8%)
Blood CPK (increase) 1 (2.3%) 3 (10.3%) 2 (5.3%) 1 (2.8%)
Oropharyngeal pain 1 (2.3%) 3 (10.3%) 1 (2.6%) 0
One SAE was reported for facial cellulitis in the 12 mg cohort; following a brief interruption, treatment was continued and this patient completed the trial.
CTP-543 Phase 3 Trial Design Overview
Phase 3 design is consistent with Phase 2 trial to support registration
Discussed key aspects of planned Phase 3 trials with FDA at End-of-Phase 2 meeting
Potential best-in-class oral treatment for alopecia areata based on Phase 2 results
Design Randomized, double-blind, placebo-controlled trial in patients with moderate-to-
severe alopecia areata
Approximately 700 patients age 18-65 years with ≥ 50% hair loss
3:3:1 randomization to CTP-543 (8 mg BID or 12 mg BID) or placebo for 24 weeks
Opportunity for completers to roll over into open label, long-term extension study
Sites: U.S., Canada and Europe
Endpoint Primary endpoint is SALT score ≤20
Secondary endpoints include patient and clinician impression scores, patient reported
outcome measures and regrowth of eyebrows and eyelashes
Status First Phase 3 expected to initiate in Q4 2020
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CTP-692: Potential First-in-Class Adjunctive Treatment in Schizophrenia
• CTP-692: deuterated D-serine (NMDA receptor co-agonist)
‒ Distinct mechanism added to existing standard of care
• Patients with schizophrenia have low levels of D-serine
• Academic studies with D-serine show benefit on
negative and cognitive symptoms of schizophrenia
as well as effects on positive symptoms
• Use of D-serine may be limited by renal safety concerns
• Deuterium improves safety profile and exposure in preclinical studies
• Phase 2 trial underway
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Schizophrenia: Prevalent, Chronic, Severe Mental Disorder
• Afflicts ~1% of the worldwide population
‒ Chronic condition affecting both men and
women equally
• Disease characterized by multiple symptoms
including:
‒ Positive symptoms – hallucinations, delusional
behaviors and thought disorder
‒ Negative symptoms – social withdrawal, flattened
affect and poverty of speech
‒ Cognitive dysfunction – diminished capacity for attention,
working memory, and executive function
• Unmet need exists to treat symptoms of schizophrenia
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Source: www.schizophrenia.com
Published Literature: D-Serine Improves Multiple Symptom Domains of Schizophrenia
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• First double-blind, placebo-controlled study as add-on to stable antipsychotic regimen
• D-serine administered 30 mg/kg per day for 6 weeks
• N = 31
Tsai et al., Biol Psychiatry, 44 (11): 1081-89, 1998
Positive Symptoms Cognitive Dysfunction Negative Symptoms
Signaling cascades regulate
neuron function
NMDA
receptor
Post-synaptic density
mGluR7
NMDA
recept
or
AMPA
receptor
mGluR3
/3
Genetic Studies Support CTP-692 Mechanism For Adjunctive Treatment of Schizophrenia
• Modern screening technology has enabled the
discovery of a set of genes associated with
schizophrenia
‒ Genes coding for glutamatergic synaptic proteins are
prominently represented
• Poor patient response to antipsychotics is
associated with mutations that impair NMDA
neurotransmission*
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Modified from Balu and Coyle, Curr Opin Pharmacol 2015
*Wang et al. JAMA Psychiatry 2018
CTP-692: Designed to Leverage D-Serine Benefits and Overcome its Limitations
• Same pharmacology as D-serine with
comparable binding and functional activity at
NMDA receptor
• D-serine is well-known to cause nephrotoxicity
in preclinical testing
• CTP-692 improved preclinical renal safety
reflected by serum creatinine and blood urea
nitrogen levels
• CTP-692 achieved higher brain concentration
relative to plasma compared to D-serine
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*N=6 for D-serine and CTP-692 except at 150mg/kg where N=12 for both
Dashed line indicates Upper Range of Normal
0
1
2
3
4
Se
rum
Cre
ati
nin
e (
mg
/dL
)
Creatinine
D-serine
CTP-692
Vehicle
0 150 250 350 450 550 650 750
(mg/kg)
NMDA Receptor Functional Activity
0 . 0 0 1 0 . 0 1 0 . 1 1 1 0 1 0 0
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
C o m p o u n d ( M )
% A
ctiv
ity
C T P - 6 9 2
D - s e r i n e
CTP-692: Phase 1 Topline Results
• Safety assessments in the SAD/MAD trials
showed CTP-692 was well tolerated over the
dose ranges tested; include doses expected to
be evaluated in Phase 2
• Key blood and urine markers of kidney function
did not indicate any signs of renal impairment
‒ Data are consistent with CTP-692 preclinical
findings indicating an improved renal safety profile
compared to non-deuterated D-serine
• CTP-692 has a well behaved PK profile
‒ D-serine is reported to be substantially variable
• Phase 1 data presented at American Society of
Clinical Psychopharmacology 2020 Annual
Meeting17
CTP-692 demonstrated a favorable safety, tolerability and PK profile with no SAEs reported
Phase 1 MAD – Day 7
0 8 16 24
0
20
40
60
80
Time (hr)
CT
P-6
92
Pla
sm
a C
on
ce
ntr
ati
on
(
g/m
L)
CTP-692_4 g
CTP-692_1 g
CTP-692_2 g
CTP-692: Phase 2 Trial
• Phase 2 evaluation underway
‒ Indication: Adjunctive treatment of schizophrenia
‒ Primary endpoint: Change in total Positive and
Negative Syndrome Scale (PANSS) score
Week 12 from baseline
‒ Inclusion: Stable on antipsychotic medication
‒ Dosing: 1, 2 and 4 grams of CTP-692 once-daily vs. placebo
‒ Number of patients: ~300 randomized
• Expect single Phase 2 to support Phase 3 development
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Strong Financial Position (Q2 2020)
Strong Validation of Platform
Successful Out Licensing
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Enhancing Value: Capital Efficiency and Strategic Agreements
• VX-561 (CTP-656) asset sale; $160 M upfront
• Up to $90 M in pre-commercial milestones
• Cash: $144.7 M
• Shares outstanding: 29.7 M
• Out-license of non-core development
provides additive value
• Downstream financial potential
Upcoming Development Milestones
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• Expect single Phase 2 to support
Phase 3 development
• Next milestone: Complete
enrollment in ongoing Phase 2 trial
✓ Conducted End-of-Phase 2 FDA
meeting Q1 2020 to support
advancement into pivotal testing
• Next milestone: Expect to initiate
Phase 3 clinical program in Q4 2020
CTP-543 for Alopecia Areata
*Pending impact of COVID-19 on development activities
CTP-692 for Schizophrenia*
Creating new possibilities for patients to live their lives
© 2020 Concert Pharmaceuticals, Inc. All Rights Reserved.
NASDAQ: CNCEwww.concertpharma.com
@ConcertPharma
For additional information contact:
Justine Koenigsberg